Antigen presentation by dendritic cells in the aortic wall triggers T helper immune responses in atherosclerosis (54.16)

Abstract

Abstract Atherosclerosis is an immune-mediated disease associated with lipid accumulation and formation of atherosclerotic plaques in the major arteries of the body. Vascular dendritic cells (DC) are present throughout the adventitia of the normal mouse aorta and expand under atherosclerotic conditions, but their function remains incompletely understood. To test whether DC can mediate productive antigen presentation directly in the aortic wall, we used two-photon microscopy. CD11cYFP tagged DC were motile in mouse aortas and interacted with T cells in an antigen dependent manner. In atherosclerotic Apoe-/- CD11cYFP mice, DC interacted with transferred T cells from Apoe-/-, but not C57BL/6 mice. Interaction with DC decreased T cell migration velocity and induced secretion of IFN-γ, TNF-α and IL-17, which enhanced oxLDL uptake by primary macrophages. Using flow cytometry of digested whole aorta from C57BL/6 and Apoe-/- mice fed either Western diet or regular chow diet, we found CD11b+CD11c+ and CD11b-CD11c+ DC in the aortic wall of C57BL/6 mice, and this population expanded in Apoe-/- mice on western diet. Under these conditions, CD8a+ and CD103 DC appear among the CD11c+ DC population. Taken together, our data show the emergence of distinct subsets of DC in the mouse aorta during the progression of atherosclerosis and demonstrate that the aortic wall can be a site of active antigen presentation leading to the induction of a pro-atherogenic immune response.